In 2005, I initiated the Protein Engineering and Molecular Design Laboratory with the ambitious goals of developing (1) “smart” protein materials capable of stimuli-responsive actuation and encapsulation of small molecules and (2) functional proteins or enzymes with a particular focus on improving stability, activity and specificity for defined substrates.

In order to achieve the successful completion of these two goals, I assembled a multidisciplinary group of highly innovative and talented individuals. The individuals range from postdoctoral researchers, graduate, undergraduate and even high school students with varying backgrounds in science and engineering disciplines. While the group is diverse, they all share the common goal of engineering proteins on the molecular level.

Jin Kim Montclare is an assistant professor in the Department of Chemical and Biological Sciences.

Together, we exploit nature’s biosynthetic machinery and evolutionary mechanisms to design new biomaterials and functional proteins. Nature has perfected the synthesis of tailor made biomolecular machines that determine the proper organization and function of organisms. Specifically, protein biosynthetic and evolutionary pathways are key processes that can be explored to develop functional molecules with precise structures. This, in combination with the chemist’s ability to produce diversity beyond nucleic acids and proteins, offers a powerful tool for the design and synthesis of new functional macromolecules. We employ cutting-edge methods of chemistry, biology and engineering with the specific aim of designing new biomaterials, therapeutic agents and biocatalysts relevant to medicine and industry. The proteins we custom-design have utility and applications in the fields of medicine, nanoelectronics and green chemistry.

Smart Protein Materials

Through billions of years of evolution, nature has produced a plethora of biomaterials
with a vast range of truly remarkable properties from serving as protection and, when compromised, self-healing to harnessing to exhibiting extreme strength and load- bearing properties. My lab exploits the protein elements that are involved in such biomaterials to fabricate unique hybrids or protein block polymers that we anticipate will share the material properties of the biomaterials in which they are based (Fig. 1).

Figure 1.

We have developed a new class of protein materials capable of: (i) hierarchical self-assembly into ordered structures from the nano- to the meso-scale; (ii) responding to external stimuli (temperature, salt, metals or pH) and effecting a change in assembly/order (molecular actuation); and (iii) performing a function (small molecule binding/release). Since we exploit recombinant DNA technology in the production of the polymers, all the biomaterials generated in our lab possess: (i) well-defined polymer sequence, composition and length from the genetic template; (ii) distinct secondary and tertiary molecular structures; (iii) the absence of harsh solvents/chemicals in the final products as they are produced by bacteria; and (iv) inherent biodegradability since they are naturally derived. Already, we have demonstrated that the protein block polymers exhibit very different structural and mechanical properties (from fluids to soft gels) depending upon the simple orientation of each protein block/domain. From this work, we are developing the materials for applications in medicine such as targeted drug delivery and tissue engineering

Engineered Functional Proteins

The central challenge in protein design is to engineer new function. Although examples of rendering proteins with novel activity and specificity exist in nature, the billion-year time-scale needed to achieve this far exceeds the lifetime of a single scientist.

Dr Montclare's lab

While tools including directed evolution, structure-based design and computational approaches have been developed to bypass natural evolution and empower the protein engineer, the ability to fashion artificial enzymes that exhibit novel substrate preferences and reactivities remains a significant obstacle. My lab has been working toward engineering functional proteins by: (i) exploiting in vivo residue-specific incorporation of unnatural amino acids (UAAs); (ii) mutagenesis in combination with UAA incorporation; and (iii) mining the natural biodiversity to identify enzymes for reactions on unnatural substrates (Fig. 2). We seek to control protein stability, activity and selectivity by these three approaches and combinations thereof. Already, we have created an assortment of proteins able to tolerate extreme heat, identify selective reactivity for desired substrates and even completely change the reactivity of an enzyme. We are further developing some of these artificial proteins as therapeutics as well as catalysts for new chemical reactions.

“Dr. Montclare really motivated me to inspire the next generation through my work." -Liz Zhao Biomolecular Science ’12 (Student fellow and teacher assistant in iPad project)”

Cultivating an Appreciation for Science and Engineering

As an extension of my interactions with students, I have been awarded funds through the Dreyfus Foundation, National Science Foundation and, most recently, the Teagle Foundation to implement a Mentored Chem-Bio Technology Lab (https://research.poly.edu/~cbtl). This outreach program expands the research experience to a larger group of students focusing on grades 6-12, especially in low-income areas such as the inner city and Brooklyn. Although my laboratory does provide a hands-on research experience to a number of high school students, it provides a solution to just a part of the problem. Studies have shown that teacher quality is critical to the success of a student in the areas of science and math. In fact, high school science and math are viewed as “gatekeeper courses” where students capable of excelling in these subjects are more likel y to succeed in high school and continue their education in college.

Figure 2.

To promote interest in science at an early level as well as assist teachers in the classroom, junior and senior undergraduate students have been recruited as paid summer fellows to create interactive modules based on modern examples in chemistry, materials science and biology. The student fellows and I have worked with Kelly DeMonaco and Kiri Soares, directors of the Urban Assembly Institute for Math and Science for Young Women (UAI), and Ben Esner, director of K-12 STEM Education, to implement interactive modules in chemistry, materials science and biology that will not only infuse technology into their curriculum, but also link the disciplines so that the students get an early glimpse of multidisciplinary science. The purpose of this project was to not only expose students to chemical sciences in the context of materials science and biology using technological aids, but to also encourage them to pursue careers in science. We have developed a number of modules that were implemented in classrooms at the UAI since 2008 that include: molecular visualization of chemical and biomolecules via Chemsketch software; hands-on experiments that introduce polymers/materials science and biodegradable materials; and the development and use of the app “LewisDots” for the iPad to teach intermolecular forces, Lewis structures as well as bonding. We also developed a STEMulus Summer Program (http://research.poly.edu/~uai/) this summer, fully supported by the Teagle Foundation. This program encompassed graduate student mentors in addition to the two undergraduate mentors to develop and implement three units on diabetes, cancer and HIV/AIDs. We combined lectures, experimentation and use of the iPad to teach 9th-10th grade girls from the UAI. At the end of the program, the students produced a final poster presentation on the topics that they studied.

“We combined lectures, experimentation and use of the iPad to teach 9th-10th grade girls from the UAI.”

As I stated in the very beginning, both research and educational programs have been successfully carried out by an excellent group of young scientists and engineers. I am most proud of my students as they have garnered over 55 awards and fellowships beyond the federal and non-federal funding supporting our research and, of this total, 40 have been awarded to NYU-Poly undergrads. There is much more to do and I look forward not only to furthering our research objectives, but also to interacting with and inspiring the next generation of scientists and engineers.

About Lewis Dots: An app created by NYU-Poly Fellow Carlo Yuvienco allows users to generate and manipulate chemical structures depicted with Lewis Dot diagrams by adding atoms to the canvas and matching their lone electrons. Dragging and dropping electrons creates single, double and triple bonds, making structures that are tedious to draw by hand simple and synchronizable to the Photos app.